Genetic disorders of keratinization will be studied to define the molecular basis of these diseases. Ichthyosis and keratosis palmaris/plantaris are the major diseases under study. The amino acid composition and molecular weight of the proteins will be determined. epsilon-(gamma-glutamyl)lysine cross-links in the epidermis will be determined and the enzyme transglutaminase which forms this cross-links isolated, quantitated and characterized. The cell envelope and its precursors will be isolated and characterized. The major methods to be used are sequential extractions with urea and disulfide reducing agents, preparation and analysis of cyanogen bromide and tryptic peptides.